著者

福岡 正喜 中西 由香 Bernhard Krautler 虎谷 哲夫

出版者

公益社団法人 日本ビタミン学会

雑誌

ビタミン (ISSN:0006386X)

巻号頁・発行日

vol.77, no.4, pp.244, 2003-04-25 (Released:2017-12-26)

著者

虎谷 哲夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.11, pp.1453-1462, 2010-11-01 (Released:2010-11-01)

参考文献数

28

被引用文献数

1 1

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Vitamin B12 is produced only by prokaryotes and utilized by animals as an essential micronutrient. Genetic complementation analysis of cell lines from patients indicated that at least eight gene products are involved in intracellular B12 metabolism and utilization. We have investigated bacterial adenosylcobalamin-dependent enzymes and elucidated their structure-based fine mechanisms. They tend to undergo mechanism-based inactivation during catalysis, because they use highly reactive radicals for catalyzing chemically difficult reactions. We have discovered molecular chaperone-like reactivating factors for these enzymes that release a damaged cofactor forming apoenzyme. Methylcobalamin-dependent methionine synthase also undergoes inactivation, because it utilizes cob(I)alamin, a super nucleophile, for catalysis. Methionine synthase reductase is a reactivating partner for this enzyme. Recent studies suggested that activity-maintaining systems for B12 enzymes are present in animal cells as well, and thus hints for designing therapeutic agents for B12-related metabolic disorders might be obtained from the investigations of microbial B12 metabolism.